Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study.

Abstract

BACKGROUND:

Oral estrogen therapy increases the risk of venous thromboembolism (VTE) in postmenopausal women. Transdermal estrogen may be safer. However, currently available data have limited the ability to investigate the wide variety of types of progestogen.

METHODS AND RESULTS:

We performed a multicenter case-control study of VTE among postmenopausal women 45 to 70 years of age between 1999 and 2005 in France. We recruited 271 consecutive cases with a first documented episode of idiopathic VTE (208 hospital cases, 63 outpatient cases) and 610 controls (426 hospital controls, 184 community controls) matched for center, age, and admission date. After adjustment for potential confounding factors, odds ratios (ORs) for VTE in current users of oral and transdermal estrogen compared with nonusers were 4.2 (95% CI, 1.5 to 11.6) and 0.9 (95% CI, 0.4 to 2.1), respectively. There was no significant association of VTE with micronized progesterone and pregnane derivatives (OR, 0.7; 95% CI, 0.3 to 1.9 and OR, 0.9; 95% CI, 0.4 to 2.3, respectively). In contrast, norpregnane derivatives were associated with a 4-fold-increased VTE risk (OR, 3.9; 95% CI, 1.5 to 10.0).

CONCLUSIONS:

Oral but not transdermal estrogen is associated with an increased VTE risk. In addition, our data suggest that norpregnane derivatives may be thrombogenic, whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk. If confirmed, these findings could benefit women in the management of their menopausal symptoms with respect to the VTE risk associated with oral estrogen and use of progestogens.

• Authors: Marianne Canonico, Emmanuel Oger, Geneviève Plu-Bureau, Jacqueline Conard, Guy Meyer, Hervé Lévesque, Nathalie Trillot, Marie-Thérèse Barrellier, Denis Wahl, Joseph Emmerich, Pierre-Yves Scarabin, Estrogen and Thromboembolism Risk (ESTHER) Study Group
• Journal: Circulation (Circulation) Vol. 115 Issue 7 Pg. 840-5 (Feb 20 2007) ISSN: 1524-4539 [Electronic] United States
• PMID: 17309934 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogens
• Hormones
• Progestins

Topics

• Administration, Cutaneous
• Administration, Oral
• Aged
• Case-Control Studies
• Drug Administration Routes
• Estrogen Replacement Therapy (adverse effects)
• Estrogens (administration & dosage)
• Female
• Hormones (administration & dosage)
• Humans
• Middle Aged
• Postmenopause
• Progestins (administration & dosage)
• Thromboembolism (chemically induced)
• Venous Thrombosis (chemically induced)